This software is also used to document the completion of manufacturing steps on batch records, including [redact] amounts, manufacturing activities, and calculations. You stated to our investigator that this [redact] software was not validated and lacked audit trails.
In addition, your firm lacked adequate controls to ensure that actions are attributed to authorized individuals with unique and unshared login credentials. For example, our investigator observed that the login credentials of employee, [redact], were used to document the completion of several manufacturing activities on two drug product batch records dated March 17, 2021, and July 19, 2021. However, you stated to our investigator that [redact] has not been employed at the company since September 2019. Further, it was observed that login credentials including “[redact]” and “[redact]” were used to document the completion of several manufacturing activities. You stated to our investigator that these login credentials were shared by multiple employees. Shared login credentials are unacceptable, as this practice prevents the identification of specific individuals accessing a controlled system.
Your quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture.
During the inspection, our investigator observed that many of your computerized systems lacked sufficient controls to ensure the integrity of the data being generated. For example:
Our investigator found “System/Administrator” as the only user role for your [redact] software. There were no restrictions on deleting or modifying data for this user role. [redact] was used for assay and identity testing of finished thyroid, USP API from March 2021 to November 2021.
Our investigator observed numerous deviations to original peak area results for HPLC assays of finished thyroid, USP API validation lots. There was no documentation of these alterations, but your quality unit personnel stated this may have been due to an unapproved update to the [redact] HPLC equipment. This equipment was never qualified according to your quality unit personnel.
A non-validated Excel spreadsheet was utilized to calculate finished thyroid, USP API assay results for all validation lot assay calculations. The formulas and outputs of the spreadsheet were printed at the time of the calculation and not saved. You were unable to provide an electronic copy of the original spreadsheet or master spreadsheet during the inspection.
Manufacturing master batch records held in electronic form on your company’s shared drive do not have restrictions on user access. Your quality unit personnel stated that there are no restrictions for any personnel with login credentials to access new and obsolete master records. Our investigator observed during the inspection multiple versions of batch records were utilized for API lot production.
Your firm failed to implement adequate controls to support the integrity of your electronic data and to ensure that only appropriate individuals had administrative rights. For example, your [redact] microbiological testing instrument used for drug product release testing is controlled by a stand-alone computer which does not have appropriate controls in place to prevent deletion of raw laboratory data. All QU users utilized a shared generic account to access the computer which had administrative privileges capable of changing and deleting files. During the inspection, one of your employees opened the computer’s recycle bin and noted that approximately [redact] files and folders were deleted. Further, these deleted items included at least [redact] files of the “[redact]” format which your personnel stated were most likely [redact] data files. The names of [redact] of those deleted files were similar to drug product formulas produced since 2017.
For multiple sterile drug product lots, your original data showed failing results, but data you reported showed passing results. This discrepancy was not adequately explained.
You stored original data in an “unofficial” and uncontrolled electronic spreadsheet on a shared computer network drive. Your analyst stated that original data was first recorded in this “unofficial” spreadsheet and transcribed later to an “official” form. This spreadsheet showed failing results above the limits you established in your procedure, PCH 035 Visible Particle Determination in use prior to September 1, 2014.
SpectrumLabs.com is a leader in the manufacture and supply of single-use hollow fiber filtration modules and tangential flow filtration systems for the Diagnostic, Bioprocessing and Pharmaceutical Industries. In addition to the largest selection of single-use hollow fiber filters, Spectrum’s KrosFlo® process filtration products include filtration systems for tangential flow filtration and bioreactor perfusion.
SpectrumLabs’s KF Comm is a software program that allows users to collect real-time data from the KR2i or KMPi pumps and auxiliary components (optional scales, pumps, and valves) in a Microsoft® Excel® spreadsheet.
The software records 12 real-time operating parameters:
Time
Inlet Pressure
Retentate Pressure
Permeate Pressure
Feed Flow Rate
Pump RPM
Pump Mode (7 different Pump modes)
Permeate Flow Rate (with optional auxiliary pump)
Notes (Alarm, Process Status, Functions)
Diafiltration Flow Rate ( with optional auxiliary pump)
Feed Scale Weight ( with optional auxiliary scale)
Permeate Scale Weight ( with optional auxiliary pump)
The software Calculates 8 parameters:
Transmembrane Pressure (TMP)
Permeate Flow Rate (with no optional auxiliary pump)
Retentate Flow Rate (with no optional auxiliary pump)
Flux
Pressure Drop (ΔP)
Volumetric Throughput (VT)
Concentration Factor
Shear
All process parameters are recorded at user-defined intervals eliminating the need for manual recording. In doing so, KF Comm enables quick analysis using Excel graphs and facilitates optimization, scale-up and process documentation. SpectrumLabs.com uses ExcelSafe™ to provide compliance with 21 CFR11 in the KF Comm software.
ExcelSafe is available for the following versions of KF Comm software;
KMPi: Process Controls and Data Collection Software for Pilot-scale Bioprocessing (more info)
KR2i: Data Collection Software for R&D Scale Bioprocessing (more info)
Pricing Information
For KF Comm to be 21 CFR Part 11 Compliant it needs to be used with a KF Comm Compliant Workbook and interface with the Ofni Systems’ ExcelSafe™ software package.
The price for a KF Comm validation package bundled with ExcelSafe is $10,995.
We also can provide a complete validation package for KF Comm. Each validation package includes a Functional Specification, Design Specification and Installation/Operational Test Protocol. The validation package also includes an example execution of the test protocol and a Validation Summary Report. There is also a separate validation package for ExcelSafe.
Validation Package for both KF Comm Software and ExcelSafe: $5,995
Validation Package for KF Comm Software only: $2,495 each
“The trial injection data was stored in the “Trial” folder located on a PC with no audit trail linked to the HPLC instrument…
The audit trail for the dissolution analysis of the 9-month long-term stability sample of [redacted] USP [redacted] mg Tablets batch [redacted] conducted on March 22, 2014, showed a single manual injection that was not included in the official test results package. A manual “trial” sample injection from vial position [redacted] at 12:29 pm was injected between the Set [redacted] and Set [redacted] analytical sequences. No deviation was documented regarding the extra sample injection. In addition, the original injection data obtained for vial position [redacted] was overwritten and not saved. Because the original data was overwritten, you did not review and evaluate it as part of your batch release decision…
Your firm failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68(b)).
FDA investigators discovered a lack of basic laboratory controls to prevent changes to electronically stored data. The following examples show that you lack effective control of the integrity of instrument output data:
The ten Shimadzu HPLC instruments in the QC “commercial” laboratory were configured to send acquired injection data to PCs without audit trails.
There was a lack of controls to prevent substitution or overwriting of data. The [redacted] audit trail dated January 6, 2014, for HPLC MLG/QC/12/026 and the [redacted] audit trail dated January 15, 2014, for HPLCs MLG/QC/12/031 and MLG/QC/12/027 each showed sample injections marked with the same small graphic symbol. For each of these entries, you replaced the original injection sequence data with data from a single manual injection and failed to save the original sequence data.
A “File Note” dated February 10, 2014, signed by the QC Head, established that the printed data used for batch disposition decisions from the Metrohm Titrando Instrument MLG/QC/12/048 hard drive was not necessarily the complete data for a batch. Our inspection found that data on the instrument was selected for use and was not protected from change and deletion. Notably, the audit trail capability of this QC “commercial” laboratory instrument was not enabled, even after creation of the “File Note.”
Tyson Mew, president of Ofni Systems, will be at the 4th Global QA Conference & 30th SQA Annual Meeting in Las Vegas, NV, from April 6–11, 2014. Ty will be demonstrating how ExcelSafe gives your analytical spreadsheets the controls and security features needed for 21 CFR Part 11 compliance.
Learn how to Create and Validate Spreadsheets in FDA-Regulated Environments
Easy-to-create and surprisingly powerful and flexible tools for data storage and processing, spreadsheets are so common that they can almost seem invisible. However, GxP data stored or processed with spreadsheets must be maintained in accordance with all applicable regulatory requirements, especially 21 CFR 11, Electronic Records Electronic Signatures. The FDA is aware of the usefulness of spreadsheets but expects controls to be in place that ensure spreadsheets used in GxP processes are compliant with 21 CFR 11 and are validated. As FDA enforcement of 21 CFR 11 increases, uncontrolled spreadsheets represent an area of increased QA concern.
Society of Quality Assurance
SQA’s 4th Global QA Conference & 30th Annual Meeting is a six-day conference for discussion of emerging trends and issues affecting Quality Assurance practices in regulated industry. Hot topics include Computer Validation, Scientific Archiving, Industry Best-Practices, and Compliance. The conference will feature a number of industry expert talks and opportunities for knowledge exchange among QA peers from around the globe.
Ty Mew and Ofni Systems will be available throughout the conference to discuss spreadsheet and software compliance and validation.
Registration information for the 14th Annual Computer and Software Validation conference is available here.
Raleigh North Carolina – Ofni Systems announces that the upcoming release of their ExcelSafe Spreadsheet compliance software application will offer support for enterprise-level document management systems including Microsoft Sharepoint and the Agilent OpenLab Enterprise Content Manager (ECM).
“This is a giant step forward for the ExcelSafe application,” stated Ty Mew, President of Ofni Systems. “The next version will be a drop-in-place solution for both existing and new ExcelSafe customers that will offer the security, convenience, and document protection of a check-out/check-in module. Users can now travel with their spreadsheets while still maintaining full FDA 21 CFR Part 11 compliance.”
The ExcelSafe software has been used at the FDA and by hundreds of pharmaceutical, medical device, and clinical companies to ensure that their spreadsheets are compliant with FDA regulations for electronic records and signatures. ExcelSafe allows these companies to use the flexibility and economy of spreadsheets to perform FDA regulated activities. ExcelSafe provides users of Microsoft Excel with:
User Security – Entry into spreadsheets requires a user name and password. ExcelSafe has configurable user-level security which can restrict which users can open or spreadsheets and apply or remove electronic signatures.
Data Security – All changes to Excel are automatically recorded. The audit trail records the previous and new value of a cell, the date/time of a change, the user making the change and the reason data was changed. The audit trail also records other spreadsheet events, including addition or deletion of a worksheet. Electronic signatures prevent changes within a worksheet. Even deleted records are preserved on an unalterable audit trail.
Traceability – ExcelSafe comes with tools to track all changes to spreadsheets. Users can query results from any spreadsheet.
Simplicity – ExcelSafe works automatically with existing spreadsheets and templates. Once a spreadsheet is opened in ExcelSafe, all compliance tools work automatically. Users operate Excel normally; there is no complicated interface to learn. ExcelSafe supports any number of users and any number of spreadsheets.
Ofni Systems is an industry leader for 21 CFR Part 11 compliance. Their products for Part 11 compliant databases and spreadsheets are used by pharmaceutical, biotech, and medical device companies across the globe, while it’s products for computer validation, auditing, and FDA submissions ensure that their clients meet every requirement for electronic records and electronic signatures. The company provides live desktop support for superior customer support and training and has been providing solutions to their clients since 1999. For more information, call (919) 844-2494 or visit www.OfniSystems.com.
MS Excel is the FDA’s software of choice for processing results, analyzing and presenting scientific data in their chemical and microbiological laboratories. The FDA, like many organizations, uses Excel to record test results and other report data, and needs compliant, password protected spreadsheets. The San Juan District Laboratory wanted to retain the power and flexibility of Excel for their analysts, while transitioning to a paperless environment and remaining compliant with 21 CFR 11. In order to achieve these goals, the San Juan District Laboratory selected ExcelSafe by Ofni Systems.
The FDA publishes an internal Laboratory Investigation Bulletin (LIB) each month that is distributed to all FDA employees. It contains articles written by FDA employees that describe methods, procedures and products that a site has used that have demonstrated a high degree of success or an improvement over an existing method. The goal of these articles is to promote best practices to other sites within the agency. In the June 2012 issue, the San Juan District Laboratory released a Laboratory Information Bulletin 4524 “Evaluation of ExcelSafe to Implement Part 11 Rules in FDA Analyst WorkBook Files” detailing their experiences with ExcelSafe.
Click Here To Download
The San Juan District Laboratory investigation showed that ExcelSafe improved the analytical spreadsheet’s application’s data integrity, security and template accountability by using electronic signatures, audit trails, and other compliance and tracking features. Using ExcelSafe improved laboratory efficiency by decreasing the time required for internal document review. They praised the ease of using ExcelSafe, noting that ExcelSafe had produced significant cost and time savings, and stated they would continue to use ExcelSafe.
Learn more about ExcelSafe
Media Contact
Ty Mew
President
Ofni Systems, Inc.
Phone: (919) 844 – 2494
About Ofni Systems
Ofni Systems is an industry leader for 21 CFR Part 11/Annex 11 compliance and automating the validation process. Started in 1999, their products for compliant databases and spreadsheets are used by the FDA, pharmaceutical, biotech and medical device companies across the globe. They are the creators of ExcelSafe for Excel spreadsheet security and the Part 11 Toolkit for compliant databases. They also are the creators of the FastVal validation software for generating and executing validation documents, and have been providing professional validation services using FastVal since 2006. The company’s products for computer validation, auditing and FDA submissions ensure that their clients meet all requirements for electronic records and electronic signatures. Ofni Systems provides live desktop support for superior customer support and training. For more information, call (919) 844-2494 or visit www.OfniSystems.com.
Raleigh North Carolina – Ofni Systems announces ExcelSafe, version 2.1, which provides MS Excel with password protection, user level security, audit trails and electronic signatures. “ExcelSafe is an excellent tool for regulated industry. It provides the technological tools to make MS Excel compliant with 21 CFR Part 11,” said Ofni Systems President Tyson Mew. “ExcelSafe is spreadsheet security made simple.”
ExcelSafe provides users of Microsoft Excel with
User Security – Entry into spreadsheets requires a user name and password. ExcelSafe has configurable user-level security which can restrict which users can open or spreadsheets and apply or remove electronic signatures.
Data Security – All changes to Excel are automatically recorded. The audit trail records the previous and new value of a cell, the date/time of a change, the user making the change and the reason data was changed. The audit trail also records other spreadsheet events, including addition or deletion of a worksheet. Electronic signatures prevent changes within a worksheet. Even deleted records are preserved on an unalterable audit trail.
Traceability – ExcelSafe comes with tools to track all changes to spreadsheets. Users can query results from any spreadsheet.
Simplicity – ExcelSafe works automatically with existing spreadsheets and templates. Once a spreadsheet is opened in ExcelSafe, all compliance tools work automatically. Users operate Excel normally; there is no complicated interface to learn. ExcelSafe supports any number of users and any number of spreadsheets.
Version 2.1 includes additional tools for users to classify spreadsheets, improved compatibility with Excel 2007 file formats and for system administrators to facilitate the use of ExcelSafe across networks. ExcelSafe can be configured to use either an Oracle or a SQL Server for data storage.
About Ofni Systems
Ofni Systems is an industry leader for 21 CFR Part 11 compliance. Their products for Part 11 compliant databases and spreadsheets are used by pharmaceutical, biotech and medical device companies across the globe, while it’s products for computer validation, auditing and FDA submissions ensure that their clients meet every requirement for electronic records and electronic signatures. The company provides live desktop support for superior customer support and training, and has been providing solutions to their clients since 1999. For more information, call (919) 844-2494 or visit www.OfniSystems.com.
Media Contact
Tyson Mew
President
Ofni Systems, Inc.
Phone: (919) 844 – 2494
, version 2.1, which provides MS Excel with password protection, user level security, audit trails and electronic signatures. “ExcelSafe is an excellent tool for regulated industry. It provides the technological tools to make MS Excel compliant with 21 CFR Part 11,” said Ofni Systems President Tyson Mew. “ExcelSafe is spreadsheet security made simple.”
